Ruthenium-Catalyzed Cycloaddition between Propargylic Alcohols and Cyclic 1,3-Dicarbonyl Compounds via an Allenylidene Intermediate

Article abstract of DOI:10.1021/jo0357465

Thiolate-bridged diruthenium complexes such as [Cp*RuCl(μ ₂-SR)₂RuCp*Cl] (Cp* = η⁵-C ₅Me₅; R = Me, ⁿPr, ⁱPr) and [Cp*RuCl(μ₂-SⁱPr)₂RuCp*(OH ₂)]OTf(OTf = OSO₂CF₃) promote the cycloaddition between propargylic alcohols and cyclic 1,3-dicarbonyl compounds to give either the corresponding 4,6,7,8-tetrahydrochromen-5-ones or 4H-cyclopenta[b]pyran-5-ones in high yields with complete regioselectivity. This catalytic cycloaddition provides a simple and one-pot synthetic protocol for a variety of substituted chromenones and cyclopenta[b]pyranones.

Full text of DOI:10.1021/jo0357465

Ru th en iu m -Ca ta lyzed Cycloa d d ition betw een P r op a r gylic
Alcoh ols a n d Cyclic 1,3-Dica r bon yl Com p ou n d s via a n
Allen ylid en e In ter m ed ia te
Yoshiaki Nishibayashi,*,† Masato Yoshikawa,† Youichi Inada,† Masanobu Hidai,‡ and
Sakae Uemura*,†
Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University,
Yoshida, Sakyo-ku, Kyoto 606-8501, and Department of Materials Science and Technology, Faculty of
Industrial Science and Technology, Tokyo University of Science, Noda, Chiba 278-8510, J apan
ynishiba@scl.kyoto-u.ac.jp; uemura@scl.kyoto-u.ac.jp
Received November 28, 2003
Thiolate-bridged diruthenium complexes such as [Cp*RuCl(µ2-SR)2RuCp*Cl] (Cp* ) η5-C5Me5; R
) Me, nPr, iPr) and [Cp*RuCl(µ2-SiPr)2RuCp*(OH2)]OTf (OTf ) OSO2CF3) promote the cycloaddition
between propargylic alcohols and cyclic 1,3-dicarbonyl compounds to give either the corresponding
4,6,7,8-tetrahydrochromen-5-ones or 4H-cyclopenta[b]pyran-5-ones in high yields with complete
regioselectivity. This catalytic cycloaddition provides a simple and one-pot synthetic protocol for a
variety of substituted chromenones and cyclopenta[b]pyranones.
SCHEME 1
In tr od u ction
Quite recently, we disclosed the ruthenium-catalyzed
efficient propargylic alkylation of propargylic alcohols
with carbon-centered nucleophiles such as ketones, â-di-
ketones, and silyl enol ethers to give the corresponding
propargylic alkylated products in high yields with quite
high regioselectivity as shown in Scheme 1 using acetone
as a representative substrate.1 It is noteworthy that the
reactions are catalyzed only by thiolate-bridged diruthe-
nium complexes2 such as [Cp*RuCl(µ2-SR)2RuCp*Cl]
CHART 1
(Cp* ) η5-C5Me5; R ) Me (1a ), Pr (1b), Pr (1c)), and
[Cp*RuCl(µ2-SiPr)2RuCp*(OH2)]OTf (OTf ) OSO2CF3)
(1d ) (Chart 1). Results of some stoichiometric and
catalytic reactions indicate that this novel propargylic
substitution reaction proceeds via allenylidene com-
plexes3 as key intermediates. Although remarkable de-
velopments of the reactivity of allenylidene complexes
have been attained, only a few examples of catalytic
reactions via allenylidene intermediates have been re-
ported until now.4 This novel ruthenium catalysis pro-
n
i
vides a versatile synthetic preparative method for the
propargylic alkylated compounds directly from propar-
gylic alcohols and a variety of ketones.1 The reaction is
considered to be a catalytic version of the Nicholas
reaction, which is well-known for propargylic alkylation,
but it needs several steps and a stoichiometric amount
of Co2(CO)8 for the preparation of these compounds.5
During our continuous study on catalytic reactions via
allenylidene intermediates,6 we have now found a novel
reaction between propargylic alcohols and cyclic 1,3-
dicarbonyl compounds to give the corresponding cyclo-
† Kyoto University.
‡ Tokyo University of Science.
(1) (a) Nishibayashi, Y.; Wakiji, I.; Ishii, Y.; Uemura, S.; Hidai, M.
J . Am. Chem. Soc. 2001, 123, 3393. (b) Nishibayashi, Y.; Onodera, G.;
Inada, Y.; Hidai, M.; Uemura, S. Organometallics 2003, 22, 873.
(2) Thiolate-bridged diruthenium complexes (1) have been found to
provide unique bimetallic reaction sites for activation and transforma-
tion of various terminal alkynes; see: Nishibayashi, Y.; Yamanashi,
M.; Wakiji, I.; Hidai, M. Angew. Chem., Int. Ed. 2000, 39, 2909 and
references therein.
(3) For recent reviews, see: (a) Werner, H. Chem. Commun. 1997,
903. (b) Touchard, D.; Dixneuf, P. H. Coord. Chem. Rev. 1998, 178-
180, 409. (c) Bruce, M. I. Chem. Rev. 1998, 98, 2797. (d) Cadierno, V.;
Gamasa, M. P.; Gimeno, J . Eur. J . Inorg. Chem. 2001, 571.
(4) For examples of catalytic reactions via allenylidene intermedi-
ates, see: (a) Trost, B. M.; Flygare, J . A. J . Am. Chem. Soc. 1992, 114,
5476. (b) Maddock, S. M.; Finn, M. G. Angew. Chem., Int. Ed. 2001,
40, 2138. (c) Yeh, K.-L.; Liu, B.; Lo, H.-L.; Huang, H.-L.; Liu, R.-S. J .
Am. Chem. Soc. 2002, 124, 6510. (d) Datt, S.; Chang, C.-L.; Yeh, K.-
L.; Liu, R.-S. J . Am. Chem. Soc. 2003, 125, 9294.
(5) For recent reviews, see: (a) Nicholas, K. M. Acc. Chem. Res. 1987,
20, 207 and references therein. (b) Caffyn, A. J . M.; Nicholas, K. M. In
Comprehensive Organometallic Chemistry II; Abel, E. W., Stone, G.
A., Wilkinson, G., Eds.; Pergamon: New York, 1995; Vol. 12, Chapter
7.1. (c) Green, J . R. Curr. Org. Chem. 2001, 5, 811. (d) Teobald, B. J .
Tetrahedron 2002, 58, 4133.
(6) (a) Nishibayashi, Y.; Wakiji, I.; Hidai, M. J . Am. Chem. Soc. 2000,
122, 11019. (b) Nishibayashi, Y.; Inada, Y.; Hidai, M.; Uemura, S. J .
Am. Chem. Soc. 2002, 124, 7900. (c) Nishibayashi, Y.; Yoshikawa, M.;
Inada, Y.; Hidai, M.; Uemura, S. J . Am. Chem. Soc. 2002, 124, 11846.
(d) Nishibayashi, Y.; Inada, Y.; Hidai, M.; Uemura, S. J . Am. Chem.
Soc. 2003, 125, 6060. (e) Nishibayashi, Y.; Yoshikawa, M.; Inada, Y.;
Milton, M. D.; Hidai, M.; Uemura, S. Angew. Chem., Int. Ed. 2003,
42, 2681. (f) Nishibayashi, Y.; Imajima, H.; Onodera, G.; Hidai, M.;
Uemura, S. Organometallics 2004, 23, 26.
10.1021/jo0357465 CCC: $27.50 © 2004 American Chemical Society
Published on Web 04/14/2004
3408
J . Org. Chem. 2004, 69, 3408-3412

Ruthenium-Catalyzed Cycloaddition
TABLE 1. Cycloa d d ition betw een P r op a r gylic Alcoh ol (2) a n d 1,3-Cycloh exa n ed ion e (3a )a
run
R
catalyst
isolated yield of 4 [%]
1
2c
3
4
5
6
7
8
9
Ph (2a )
Ph (2a )
Ph (2a )
Ph (2a )
Ph (2a )
p-MeC6H4 (2b)
p-ClC6H4 (2c)
p-MeOC6H4 (2d )
p-CF3C6H4 (2e)
2-naphthyl (2f)
Ph2CdCH (2g)
[Cp*RuCl(µ2-SMe)2Cp*RuCl] (1a )
[Cp*RuCl(µ2-SMe)2Cp*RuCl] (1a )
[Cp*RuCl(µ2-SnPr)2Cp*RuCl] (1b)
[Cp*RuCl(µ2-SiPr)2Cp*RuCl] (1c)
[Cp*RuCl(µ2-SiPr)2Cp*Ru(OH2)]OTf (1d )d
[Cp*RuCl(µ2-SMe)2Cp*RuCl] (1a )
[Cp*RuCl(µ2-SMe)2Cp*RuCl] (1a )
[Cp*RuCl(µ2-SMe)2Cp*RuCl] (1a )
[Cp*RuCl(µ2-SMe)2Cp*RuCl] (1a )
[Cp*RuCl(µ2-SMe)2Cp*RuCl] (1a )
[Cp*RuCl(µ2-SMe)2Cp*RuCl] (1a )
4a , 93 (>95)b
4a , (83)b
4a , (88)b
4a , (20)b
4a , (25)b
4b, 91
4c, 99
4d , 94
4e, 86
4f, 98
10
11
4g, 87
a
All of the reactions between 2 (0.10 mmol) and 3a (0.50 mmol) were carried out in the presence of catalyst (0.005 mmol) and NH4BF4
(0.010 mmol) in ClCH2CH2Cl (3 mL) at 60 °C for 1 h. GLC yield. c At room temperature for 1 h. In the absence of NH4BF4.
b
d
SCHEME 2
for this catalytic cycloaddition. The use of various pro-
pargylic alcohols resulted in the formation of the corre-
sponding 4-aryl- and 4-alkenyl-substituted 4,6,7,8-tet-
rahydrochromen-5-ones (4b-g) in excellent yields with
complete regioselectivity (Table 1; runs 6-11). Unfortu-
nately, the reactions of 1-cyclohexyl-2-propyn-1-ol and
1,1-diphenyl-2-propyn-1-ol with 3a did not proceed at all.
addition products such as 4,6,7,8-tetrahydrochromen-5-
ones (Scheme 2) and 4H-cyclopenta[b]pyran-5-ones in
high yields with complete regioselectivity. This catalytic
cycloaddition provides a simple and one-pot synthetic
protocol for a variety of substituted chromenones and
pyranones. We describe here the results of the unprec-
edented cycloaddition catalyzed only by thiolate-bridged
diruthenium complexes.
Reactions of 2a with other cyclic and acyclic 1,3-
diketones were investigated in the presence of 1a (5 mol
%) and NH4BF4 (10 mol %) in 1,2-dichloroethane at
60 °C for 1 h. Typical results are shown in Table 2. 7,7-
Dimethyl-4-phenyl-4,6,7,8-tetrahydrochromen-5-one (4h )
was formed in high yield in the reaction of 2a with 5,5-
dimethyl-1,3-cyclohexanedione (3b) (Table 2; run 1). The
reaction of 2a with 1,3-cyclopentanedione (3c) gave
4-phenyl-6,7-dihydro-4H-cyclopenta[b]pyran-5-one (4i) in
98% isolated yield (Table 2; run 2). In sharp contrast,
only a propargylic alkylated compound (7a or 7b1a) was
obtained selectively in moderate yield when the reaction
of 2a with 1,3-cycloheptanedione (3d ) or acetylacetone
(3e) was carried out under the same reaction conditions
(Table 2; runs 3 and 4).
Resu lts a n d Discu ssion
Treatment of 1-phenyl-2-propyn-1-ol (2a ) with 1,3-
cyclohexanedione (3a ) in the presence of 1a (5 mol %)
and NH4BF4 (10 mol %) in 1,2-dichloroethane at 60 °C
for 1 h afforded 4-phenyl-4,6,7,8-tetrahydrochromen-5-
one (4a ) in 93% isolated yield (>95% GLC yield) (Table
1; run 1). The molecular structure of 4a was unambigu-
ously clarified by X-ray analysis. Neither other products
nor regioisomers of 4a were detected by GLC and 1H
NMR. The reaction proceeded quite smoothly even at
room temperature for 1 h, with 4a being obtained in 83%
GLC yield (Table 1; run 2). The kind of a bridging thiolato
ligand in the diruthenium complex was found to have a
strong influence on the catalytic activity. Thus, the
complex bearing a sterically demanding SiPr group
[Cp*RuCl(µ2-SiPr)2RuCp*Cl] (1c) exhibited only low cata-
lytic activity, while the complex bearing a SnPr group
[Cp*RuCl(µ2-SnPr)2RuCp*Cl] (1b) showed almost the
same catalytic activity as 1a (Table 1; runs 3 and 4). The
catalytic activity of cationic complexes7 such as [Cp*RuCl-
(µ2-SiPr)2RuCp*(OH2)]OTf (1d ) was similar to that of the
neutral complexes (Table 1; run 5). Other di- and
monoruthenium complexes such as [Cp*RuCl(PPh3)2],
[RuCl2(PPh3)3], [RuCl2(p-cymene)]2, [(indenyl)RuCl-
(PPh3)2], and [Cp*RuCl(µ2-Cl)2RuCp*Cl] were ineffective
Next, reactions of propargylic alcohols with cyclic
â-keto esters were similarly examined. The reaction of
2a with tetronic acid (tetrahydrofuran-2,4-dione) (3f) in
the presence of 1a (5 mol %) at 60 °C for 1 h gave
4-phenyl-4,7-dihydrofuro[3,4-b]pyran-5-one (4j) in 83%
isolated yield with complete regioselectivity (Table 2; run
5). The molecular structure of 4j was unambiguously
clarified by X-ray analysis. The corresponding 4,7-dihy-
drofuro[3,4-b]pyran-5-ones were obtained from various
aryl- and alkenyl-substituted propargylic alcohols (4k -
m ) in high yields (Table 2; runs 6-8). A â-keto ester with
six-membered ring, 4-hydroxycoumarin (3g), reacted with
2a under the same reaction conditions to afford 4-phenyl-
4H-pyrano[3,2-c]chromen-5-one (4n ) in an excellent yield
without the formation of other isomers (Table 2; run 9).
Interestingly, the reaction of 2a with an acyclic â-keto
ester, methyl acetoacetate (3h ), afforded the correspond-
ing propargylic alkylated product as a mixture of two
diastereoisomers (Table 2; run 10), but in low yield. It is
noteworthy that the cycloaddition proceeded selectively
only when cyclic 1,3-dicarbonyl compounds with five- and
six-membered rings were used. On the other hand, double
(7) (a) Inada, Y.; Nishibayashi, Y.; Hidai, M.; Uemura, S. J . Am.
Chem. Soc. 2002, 124, 15172. (b) Nishibayashi, Y.; Inada, Y.; Hidai,
M.; Uemura, S. Angew. Chem., Int. Ed. 2003, 42, 1495.
J . Org. Chem, Vol. 69, No. 10, 2004 3409

Nishibayashi et al.
TABLE 2. Rea ction s of P r op a r gylic Alcoh ol (2a ) w ith Cyclic a n d Acyclic 1,3-Dica r bon yl Com p ou n d s (3)a
a
All of the reactions of 2a (0.60 mmol) with 3 (3.00 mmol) were carried out in the presence of 1a (0.03 mmol) and NH4BF4 (0.06 mmol)
in ClCH2CH2Cl (18 mL) at 60 °C for 1 h. For 20 h. c 2b was used in place of 2a . 2c was used in place of 2a . e 2g was used in place of
b
d
2a . f Two diastereoisomers were formed in an isomer ratio of 1:1. A mixture of unidentified compounds was formed.
g
propargylation occurred at the R-position of meldrum’s
acid (2,2-dimethyl-1,3-dioxane-4,6-dione) (3i) to give the
corresponding dialkylated product in 44% isolated yield
(Table 2; run 11). The reaction of 2a with dimethyl
malonate (3j) gave only a mixture of unidentified prod-
ucts, although the starting propargylic alcohol 2a was
completely consumed (Table 2; run 12).
reactions were investigated. Treatment of the alle-
nylidene complex (5), which was prepared from the
reaction of 1a with 1 equiv of 2a in the presence of NH4-
BF4 in tetrahydrofuran (THF) at room temperature for
30 min,1a with 5 equiv of 3a in 1,2-dichloroethane at 60
°C for 1 h led to the formation of 4a in 61% GLC yield
(eq 1). Furthermore, the reaction of 2a with 3a in the
presence of 5 mol % 5 at 60 °C for 1 h afforded 4a in 96%
GLC yield. These results indicate that the cycloaddition
To elucidate the reaction mechanism of the cycloaddi-
tion reaction, the following stoichiometric and catalytic
3410 J . Org. Chem., Vol. 69, No. 10, 2004

Ruthenium-Catalyzed Cycloaddition
SCHEME 3
of propargylic alcohols with cyclic 1,3-dicarbonyl com-
pounds proceeds via allenylidene intermediates such as
5.8
SCHEME 4
When the reaction of 2a with 3a was carried out in
the presence of 1c (5 mol %) at room temperature for 1
h in 1,2-dichloroethane, the corresponding propargylic
alkylated product (6a )9 was isolated in 28% yield together
with a small amount of 4a (eq 2),
dicarbonyl compounds to afford the corresponding chro-
men-5-ones and pyran-5-ones in high to excellent yields
with high regioselectivity. Some mechanistic studies
indicate that the catalytic cycloaddition proceeds via
allenylidene intermediates. This novel catalytic reaction
also provides a simple and efficient one-pot synthetic
protocol for a new type of skeleton of substituted chrome-
nones and pyranones.
while the treatment of 6a in the same solvent in the
presence of 1a (5 mol %) at 60 °C for 1 h gave 4a in 65%
isolated yield (eq 3).
Exp er im en ta l Section
Syn th esis of Su bstr a tes. Thiolate-bridged diruthenium
complexes2 (1) and the allenylidene complex1a (5) were pre-
pared according to our previous procedures. Propargylic alcohol
(2a ) was a commercial product. Other propargylic alcohols
were prepared by the reactions of the corresponding aldehydes
with ethynylmagnesium bromide.
These results indicate that the catalytic cycloaddition
proceeds via an initial propargylic alkylation. On the
basis of these findings, a pathway for this cycloaddition
is proposed in Scheme 3. The first step is the nucleophilic
attack of the carbon atom of 2-position of 1,3-cyclohex-
anedione to the Cγ atom of the allenylidene complex A
to give a vinylidene complex B,10 which is transformed
into an alkenyl complex C by an intramolecular nucleo-
philic attack of the oxygen atom of hydroxyl group of an
enol to the CR atom of B.11,12 In the case of the reaction
of 2a with an acyclic â-diketone 3e in the presence of 1a ,
the hydrogen bonding in D may inhibit a nucleophilic
attack of the oxygen atom, leading to the formation of
only the propargylic alkylated compound (Scheme 4).
Thus, the formation of a rigid structure, which facilitates
the nucleophilic attack of the oxygen atom in the vi-
nylidene complex B, is considered to be a driving force
to promote the cycloaddition.
R u t h en iu m -Ca t a lyzed Cycloa d d it ion b et w een P r o-
par gylic Alcoh ols an d Cyclic 1,3-Dicar bon yl Com pou n ds.
A typical experimental procedure for the reaction of 1-phenyl-
2-propyn-1-ol (2a ) with 1,3-cyclohexanedione (3a ) catalyzed by
[Cp*RuCl(µ2-SMe)2RuCp*Cl] (1a ) is described below. In a 20
mL flask were placed 1a (19 mg, 0.03 mmol) and NH4BF4 (6
mg, 0.06 mmol) under N2. Anhydrous ClCH2CH2Cl (15 mL)
was added, and then the mixture was magnetically stirred at
room temperature. After the addition of 2a (79 mg, 0.60 mmol)
and 3a (336 mg, 3.00 mmol), the reaction flask was kept at 60
°C for 1 h. The solvent was concentrated under reduced
pressure by an aspirator, and then the residue was purified
by TLC (SiO2) with EtOAc-hexane (1/9) as an eluent to give
4-phenyl-4,6,7,8-tetrahydrochromen-5-one (4a ) as yellow crys-
tals, 93.0-94.0 °C (126 mg, 0.56 mmol, 93% yield).
4-P h en yl-4,6,7,8-tetr ah ydr och r om en -5-on e (4a): 1H NMR
(270 MHz, CDCl3) δ 1.90-2.02 (m, 2H), 2.28-2.33 (m, 2H),
4.34 (d, 1H, J ) 4.6 Hz), 5.16 (dd, 1H, J ) 4.6 and 5.8 Hz),
6.48 (d, 1H, J ) 5.8 Hz), 7.14-7.28 (m, 5H). 13C NMR (67.5
Hz, CDCl3) δ 20.3, 27.6, 33.8, 37.0, 109.3, 113.7, 126.2, 127.8,
128.1, 137.9, 145.0, 165.9, 197.0. IR (KBr, cm-1) 1609 (CdC),
1651 (CdC), 1676 (CdO). Anal. Calcd for C15H14O2: C, 79.62;
H, 6.24. Found: C, 79.34; H, 6.33.
Con clu sion
We have now found a novel ruthenium-catalyzed
cycloaddition between propargylic alcohols and cyclic 1,3-
Spectroscopic data and isolated yields of other products are
as follows.
4-(4-Met h ylp h en yl)-4,6,7,8-t et r a h yd r och r om en -5-on e
(4b): Yield 91%. Colorless crystals, 106.2-107.2 °C. H NMR
1
(8) (a) Esteruelas, M. A.; Go´mez, A. V.; Lo´pez, A. M.; On˜ate, E.
Organometallics 1998, 17, 3567. (b) Bernad, D. J .; Esteruelas, M. A.;
Lo´pez, A. M.; Oliva´n, M.; On˜ate, E.; Puerta, M. C.; Valerga, P.
Organometallics 2000, 19, 4327.
δ 1.89-1.99 (m, 2H), 2.28 (s,3H), 2.29-2.33 (m, 2H), 2.45-
2.51 (m, 2H), 4.30 (d, 1H, J ) 4.7 Hz), 5.15 (dd, 1H, J ) 4.7
Hz and J ) 6.0 Hz), 6.48 (d, 1H, J ) 6.0 Hz), 7.07 (d, 2H, J )
8.1 Hz), 7.18 (d, 2H, J ) 8.1 Hz). 13C NMR δ 20.1, 20.9, 27.4,
33.3, 36.9, 109.4, 113.9, 127.8, 128.9, 135.8, 137.8, 142.3, 165.9,
197.2. Anal. Calcd for C16H16O2: C, 79.97; H, 6.71. Found: C,
79.84; H, 6.71.
(9) White solid. 1H NMR δ 1.90-2.00 (m, 2H), 2.04 (s, 1H), 2.38-
2.52 (m, 4 H), 2.57 (d, 1H, J ) 2.5 Hz), 5.49 (d, 1H, J ) 2.5 Hz), 7.19-
7.32 (m, 3H), 7.39-7.42 (m, 2H).
(10) Esteruelas, M. A.; Go´mez, A. V.; Lo´pez, A. M.; Modrego, J .;
On˜ate, E. Organometallics 1997, 16, 5826.
(11) (a) Trost, B. M.; Rhee, Y. H. J . Am. Chem. Soc. 2002, 124, 2528.
(b) Trost, B. M.; Rhee, Y. H. J . Am. Chem. Soc. 2003, 125, 7482.
(12) Gulias, M.; Rodriguez, J . R.; Castedo, L.; Mascaren˜as, J . L. Org.
Lett. 2003, 5, 1975.
4-(4-Ch lor op h en yl)-4,6,7,8-t et r a h yd r och r om en -5-on e
(4c): Yield 99%. White solid, 104.0-104.5 °C. 1H NMR δ 1.90-
2.01 (m, 2H), 2.28-2.34 (m, 2H), 2.47-2.53 (m, 2H), 4.31 (d,
J . Org. Chem, Vol. 69, No. 10, 2004 3411

Nishibayashi et al.
1H, J ) 4.7 Hz), 5.13 (dd, 1H, J ) 4.7 Hz and J ) 6.0 Hz),
6.51 (d, 1H, J ) 6.0 Hz), 7.23 (s, 4H). 13C NMR δ 20.1, 27.4,
33.3, 36.8, 108.8, 113.4, 128.2, 129.4, 132.0, 138.3, 143.6, 166.2,
197.2. Anal. Calcd for C15H13ClO2: C, 69.10; H, 5.03. Found:
C, 69.13; H, 5.09.
Hz), 7.13 (d, 2H, J ) 8.0 Hz), 7.19 (d, 2H, J ) 8.0 Hz). 13C
NMR δ 20.9, 33.6, 65.5, 103.7, 108.3, 127.8, 129.2, 136.9, 138.7,
139.2, 168.2, 171.0. Anal. Calcd for C14H12O3: C, 73.67; H, 5.30.
Found: C, 73.45; H, 5.32.
4-(4-Ch lor op h e n yl)-4,7-d ih yd r ofu r o[3,4-b]p yr a n -5-
1
4-(4-Me t h oxyp h e n yl)-4,6,7,8-t e t r a h yd r och r om e n -5-
on e (4l): Yield 80%. White solid, 143.0-144.0 °C. H NMR δ
1
on e (4d ): Yield 94%. Colorless solid, 92.2-93.5 °C. H NMR
4.33 (s, 1H), 4.70-4.72 (m, 2H), 5.13-5.18 (m, 1H), 6.65-6.69
(m, 1H), 7.23-7.33 (m, 4H). 13C NMR δ 33.5, 65.6, 103.3, 107.7,
128.7, 129.3, 133.1, 139.7, 140.1, 168.4, 170.8. Anal. Calcd for
δ 1.89-1.97 (m, 2H), 2.28-2.33 (m, 2H), 2.45-2.51 (m, 2H),
3.74 (s,3H), 4.28 (d, 1H, J ) 4.7 Hz), 5.15 (dd, 1H, J ) 4.7 Hz
and J ) 6.2 Hz), 6.49 (d, 1H, J ) 6.2 Hz), 6.80 (d, 2H, J ) 8.7
Hz), 7.21 (d, 2H, J ) 8.7 Hz). 13C NMR δ 20.1, 27.4, 32.8, 36.9,
55.0, 109.4, 113.5, 114.0, 128.9, 137.4, 137.8, 158.0, 165.8,
197.3. Anal. Calcd for C16H16O3: C, 74.98; H, 6.29. Found: C,
74.70; H, 6.43.
C
13H9ClO3: C, 62.79; H, 3.65. Found: C, 62.79; H, 3.55.
4-(2,2-Dip h en ylvin yl)-4,7-d ih yd r ofu r o[3,4-b]p yr a n -5-
1
on e (4m ): Yield 87%. White solid, 143.5-144.3 °C. H NMR
δ 3.92-3.95 (m, 1H), 4.63 (s, 2H), 4.91 (dd, 1H, J ) 3.6 Hz
and J ) 6.0 Hz), 5.85 (d, 1H, J ) 9.9 Hz), 6.45 (d, 1H, J ) 6.0
Hz), 7.15-7.48 (m, 10H). 13C NMR δ 29.0, 65.6, 103.1, 107.7,
127.3, 127.4, 127.5, 127.8, 128.0, 128.3, 129.3, 139.0, 139.0,
141.5, 143.0, 168.8, 171.1. Anal. Calcd for C21H16O3: C, 79.73;
H, 5.10. Found: C, 79.52; H, 5.19.
4-(4-T r i flu o r o m e t h y lp h e n y l)-4,6,7,8-t e t r a h y d r o -
ch r om en -5-on e (4e): Yield 86%. Colorless crystals, 106.2-
106.7 °C. 1H NMR δ 1.91-2.06 (m, 2H), 2.31-2.36 (m, 2H),
2.50-2.60 (m, 2H), 4.41 (d, 1H, J ) 4.5 Hz), 5.15 (dd, 1H, J )
4.5 Hz and J ) 6.0 Hz), 6.54 (d, 1H, J ) 6.0 Hz), 7.41 (d, 2H,
J ) 8.1 Hz), 7.53 (d, 2H, J ) 8.1 Hz). 13C NMR δ 20.3, 27.6,
34.0, 37.0, 108.6, 113.3, 124.3 (d, J ) 271 Hz). Anal. Calcd for
4-P h en yl-4H -p yr a n o[3,2-c]ch r om en -5-on e (4n ): Yield
97%. Colorless crystals, 152.0-152.5 °C. 1H NMR δ 4.51 (d,
1H, J ) 4.6 Hz), 5.32 (dd, 1H, J ) 4.6 Hz and J ) 6.1 Hz),
6.75 (d, 1H, J ) 6.1 Hz), 7.17-7.39 (m, 7H), 7.46-7.52 (m,
1H), 7.77-7.80 (m, 1H). 13C NMR δ 35.3, 103.5, 108.7, 114.1,
116.5, 122.5, 123.9, 126.9, 128.2, 128.3, 131.7, 137.9, 143.3,
152.3, 155.4, 161.2. Anal. Calcd for C18H12O3: C, 78.25; H, 4.38.
Found: C, 78.11; H, 4.44.
2-(1-P h en ylp r op yn -2-yl)cycloh ep t a n e-1,3-d ion e (7a ):
Yield 34%. Colorless crystals, 115.1-115.5 °C. 1H NMR δ
1.75-1.90 (m, 2H), 2.05-2.16 (m, 2H), 2.22 (d, 1H, J ) 2.4
Hz), 2.30-2.35 (m, 2H), 2.56-2.69 (m, 2H), 4.53 (d, 1H, J )
8.7 Hz), 4.59 (dd, 1H, J ) 2.4 Hz and J ) 8.7 Hz), 7.19-7.31
(m, 3H), 7.35-7.39 (m, 2H). 13C NMR δ 24.7, 24.9, 34.4, 44.5,
44.6, 71.6, 72.3, 83.9, 127.3, 128.3, 128.5, 138.2, 202.8, 203.3.
IR (KBr, cm-1) 1697 (CdO), 1724 (CdO), 2115 (CtC), 3280
(tC-H). Anal. Calcd for C16H16O2: C, 79.97; H, 6.71. Found:
C, 79.83; H, 6.75.
C
16H13F3O2: C, 65.30; H, 4.45. Found: C, 65.01; H, 4.50.
4-(2-Na p h th yl)-4,6,7,8-tetr a h yd r och r om en -5-on e (4f):
Yield 98%. Colorless crystals, 115.2-116.0 °C. 1H NMR δ
1.89-1.99 (m, 2H), 2.27-2.32 (m, 2H), 2.47-2.54 (m, 2H), 4.51
(d, 1H, J ) 4.7 Hz), 5.21 (dd, 1H, J ) 4.7 Hz and J ) 6.0 Hz),
6.54 (d, 1H, J ) 6.0 Hz), 7.36-7.47 (m, 3H), 7.71-7.80 (m,
4H). 13C NMR δ 20.2, 27.5, 34.0, 36.9, 109.2, 113.8, 125.3,
125.8, 126.5, 126.5, 127.5, 127.8, 127.9, 132.3, 133.4, 138.2,
142.5, 166.1, 197.3. Anal. Calcd for C19H16O2: C, 82.58; H, 5.84.
Found: C, 82.60; H, 5.86.
4-(2,2-Dip h e n ylvin yl)-4,6,7,8-t e t r a h yd r och r om e n -5-
on e (4g): Yield 87%. Yellow oil. 1H NMR δ 1.90-1.98 (m, 2H),
2.23-2.48 (m, 4H), 3.91 (dd, 1H, J ) 4.8 Hz and J ) 9.3 Hz),
4.87 (dd, 1H, J ) 4.8 Hz and J ) 5.7 Hz), 5.78 (d, 1H, J ) 9.3
Hz), 6.32 (d, 1H, J ) 5.7 Hz), 7.15-7.20 (m, 5H), 7.27-7.32
(m, 1H), 7.36-7.46 (m, 4H). 13C NMR δ 20.3, 27.5, 28.6, 37.0,
107.7, 113.1, 126.9, 127.1, 127.9, 128.1, 129.8, 131.3, 138.1,
139.6, 140.1, 142.0, 166.5, 197.5. Anal. Calcd for C23H20O2: C,
84.12; H, 6.14. Found: C, 84.08; H, 6.44.
2-Acetyl-3-p h en ylp en t-4-yn oic Acid Meth yl Ester
(7c): Yield 24%. A colorless oil. Two diastereoisomers with a
1
ratio of 54:46. H NMR δ 1.96 and 2.37 (s each, 3H), 2.29 and
2.30 (d each, 1H, J ) 2.4 Hz), 3.51 and 3.78 (s each, 3H), 3.95
and 4.01 (d each, 1H, J ) 10.5 Hz), 4.40 and 4.44 (dd each,
1H, J ) 2.4 Hz and J ) 10.5 Hz), 7.24-7.38 (m, 5H). 13C NMR
δ 29.9 and 30.7, 36.8 and 36.9, 52.3 and 52.7, 65.9 and 66.3,
72.0 and 72.6, 82.7 and 83.0, 127.8, 128.0, 128.2, 128.7, 128.8,
137.5, 167.0 and 167.4, 200.1 and 200.4. IR (neat, cm-1) 1721
(CdO), 1748 (CdO), 2117 (CtC), 3285 (tC-H). Anal. Calcd
for C14H14O3: C, 73.03; H, 6.13. Found: C, 73.04; H, 6.14.
2,2-Dim eth yl-5,5-bis(1-ph en ylpr opyn -2-yl)-[1,3]dioxan e-
4,6-d ion e (7d ): Yield 44%. White crystals, 160.7-161.2 °C.
1H NMR δ 0.46 (s, 6H), 2.65 (d, 2H, J ) 2.7 Hz), 5.10 (d, 2H,
J ) 2.7 Hz), 7.27-7.35 (m, 6H), 7.40-7.43 (m, 4H). 13C NMR
δ 28.2, 44.7, 63.4, 74.8, 80.3, 106.1, 128.6, 129.0, 129.6, 135.0,
164.4. IR (KBr, cm-1) 1744 (CdO), 1767 (CdO), 2119 (CtC),
3267 (tC-H), 3296 (tC-H). Anal. Calcd for C24H20O4: C,
77.40; H, 5.41. Found: C, 77.41; H, 5.42.
7,7-Dim et h yl-4-p h en yl-4,6,7,8-t et r a h yd r och r om en -5-
1
on e (4h ): Yield 94%. Pale yellow crystals, 84.8-85.2 °C. H
NMR δ 1.00 (s, 3H), 1.07 (s, 3H), 2.18 (d, 2H, J ) 9.2 Hz),
2.37 (s, 2H), 4.31 (d, 1H, J ) 4.6 Hz), 5.16 (dd, 1H, J ) 4.6 Hz
and J ) 5.8 Hz), 6.48 (d, 1H, J ) 5.8 Hz), 7.13-7.16 (m, 1H),
7.24-7.29 (m, 4H). 13C NMR δ 27.5, 29.0, 31.9, 34.0, 41.2, 50.7,
109.3, 112.5, 126.3, 127.8, 128.1, 137.9, 145.0, 164.2, 196.9.
Anal. Calcd for C17H18O2: C, 80.28; H, 7.13. Found: C, 80.01;
H, 7.08.
4-P h e n yl-6,7-d ih yd r o-4H -cyclop e n t a [b]p yr a n -5-on e
(4i): Yield 98%. Orange crystals, 91.8-92.2 °C. 1H NMR δ
2.35-2.38 (m, 2H), 2.60-2.64 (m, 2H), 4.29 (d, 1H, J ) 3.8
Hz), 5.13 (dd, 1H, J ) 3.8 Hz and J ) 5.8 Hz), 6.60 (d, 1H, J
) 5.8 Hz), 7.19-7.21 (m, 1H), 7.28-7.32 (m, 4H). IR (KBr,
cm-1) 1618 (CdC), 1655 (CdC), 1694 (CdO). Anal. Calcd for
C
14H12O2: C, 79.22; H, 5.70. Found: C, 79.07; H, 5.68.
4-P h en yl-4,7-d ih yd r ofu r o[3,4-b]p yr a n -5-on e (4j): Yield
Ack n ow led gm en t. This work was supported by a
Grant-in-Aid for Scientific Research for Young Scientists
(A) (No. 15685006) from the Ministry of Education,
Culture, Sports, Science and Technology, J apan.
83%. Colorless crystals, 138.1-138.3 °C. 1H NMR δ 4.35 (d,
1H, J ) 3.5 Hz), 4.73 (s, 2H), 5.20 (dd, 1H, J ) 3.5 Hz and J
) 5.9 Hz), 6.67 (d, 1H, J ) 5.9 Hz), 7.23-7.37 (m, 5H). 13C
NMR δ 34.2, 65.7, 103.8, 108.3, 127.3, 127.9, 128.6, 139.3,
141.5, 152.4, 168.1. Anal. Calcd for C13H10O3: C, 72.89; H, 4.71.
Found: C, 72.73; H, 4.81.
Su p p or tin g In for m a tion Ava ila ble: Tables and figures
giving crystallographic data for 4a and 4j; crystallographic
data are also available as CIF files. This material is available
free of charge via the Internet at http://pubs.acs.org.
4-(4-Me t h ylp h e n yl)-4,7-d ih yd r ofu r o[3,4-b]p yr a n -5-
1
on e (4k ): Yield 89%. Yellow solid, 140.2-141.0 °C. H NMR
δ 2.31 (s, 3H), 4.29 (d, 1H, J ) 3.5 Hz), 4.60-4.67 (m, 2H),
5.15 (dd, 1H, J ) 3.5 Hz and J ) 6.0 Hz), 6.62 (d, 1H, J ) 6.0
J O0357465
3412 J . Org. Chem., Vol. 69, No. 10, 2004